Lack of Correlation of Human Fibroblast Radiosensitivity in Vitro with Early Skin Reactions in Patients Undergoing Radiotherapy

Abstract

Fibroblasts from breast cancer patients were obtained as outgrowths in vitro from punch biopsies and their radiosensitivity tested in early passages. Skin erythema reactions in the same patients were also measured, as degree of redness using reflectance spectrophotometry. Measurements were taken before and during a 4-week radiotherapy treatment with electrons to the thoracic wall. Of 59 biopsies studied, radiosensitivity and erythema were concurrently studied in 32. In 24, evaluable data from both clinic and laboratory were obtained. A population growth assay in 96-well plates, using absorption of sulphur rhodamine B as the stain for cell numbers, showed good agreement with the colony-formation assay. Plating efficiencies and growth rates in the colony assay were higher using human serum in place of foetal calf serum. Cell survival curves with human serum were mostly exponential with little shoulder. The parameters of survival at 2 Gy (SF₂) and the dose required to give 10% survival (D₁₀) were used in the correlations with clinical data; these were 0·25 ± 0·09 and 3·03 ± 0·50 Gy, respectively. There was a strong correlation between these two survival curve parameters (r = 0·98). Skin redness was found to linearly increase with time during radiotherapy. The slope of the increase differed markedly from patient to patient, with a range of a factor approx. 10. No correlation was found between SF₂ and erythema response in the 24 evaluable patients (r = 0·13, p > 0·5). A similar lack of correlation was found using D₁₀ as the radio-sensitivity parameter (r = 0·12, p > 0·5). These data indicate that fibroblast radiosensitivity measured in vitro cannot be used to predict erythema reactions to radiotherapy in breast cancer patients.